Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer and birth defects. Currently under investigation are the inherited breast and ovarian cancer genes, BRCA1 and BRCA2. The biological function of these proteins is currently unknown. Previously we discovered which proteins specifically interact with BRCA1. In the past year we have found that BRCA1 is important for controlling the expression of other genes and is plays a role in DNA repair. Recent experiments has revealed that BRCA1 appears to help in the process of recognizing and eliminating cells that may progress to form tumors. We now know that the increase in breast, ovarian and prostate cancer risk associated with genetic variants in these genes is due to a failure of these mutated proteins to function in the DNA repair pathway. We are using yeast cells as an experimental model to test the functional consequences of mutations found in humans. We have also developed a system for identifying proteins that interact with BRCA1. An increased understanding of the BRCA1 and BRCA2 genes will lead to improved diagnostic procedures and possible preventative therapies.